Infection with influenza virus is responsible for a great deal of morbidity and mortality worldwide. In non-pandemic years, 10-20% of the population in the US is infected with influenza virus. In any given year, more than 120,000 persons are hospitalized and 36,000 Americans die from influenza and influenza-related complications. In the case of an influenza pandemic, each of these measures of morbidity and mortality would greatly increase. With the expectation of a pandemic influenza outbreak in the near future, it is extremely important to determine if obese individuals are at an increased risk for vaccine failure. Several published studies showing diminished antibody response to vaccination with hepatitis B in obese adults and diminished antibody response to tetanus vaccination in obese children and our own preliminary data in obese adults, suggests that obese individuals are at increased risk for higher rates of influenza vaccine failure. This proposal is designed to determine if the obese population has a diminished response to influenza vaccination. The elderly population has a higher rate of vaccine failure compared to a younger population, and many of the immune dysfunctions seen in the elderly (reduced antibody responses, impaired T cell reactivity) have also been found in the obese. This suggests that, similar to an aging population, an obese population may not respond adequately to flu vaccination. Our study will answer the following questions relating to vaccine responsiveness in an obese population: Does influenza vaccination protect an obese population from influenza infection to the same degree as a lean population? Is the response to influenza vaccine, measured by production of antibody as well as the ability of T cells to respond to influenza antigen, impaired in an obese population? Can levels and/or characteristics of the chronic inflammatory stress proteins found in obese individuals differentiate between those who respond to influenza vaccination and those that don't? If we determine that obesity is associated with an impaired immune response to influenza vaccination and decreased protection against influenza infection, this would suggest that we need to re-evaluate our vaccination program, not only for influenza, but perhaps for other pathogens as well, in an increasingly obese US population. PUBLIC HEALTH RELEVANCE: Rates of obesity are increasing rapidly worldwide resulting in major impacts on health status and disease prevention. Additionally, the threat of pandemic influenza has grown in recent years with the discovery of new strains and an increasingly susceptible population. Determination of influenza vaccination effectiveness in the obese population will provide an invaluable resource in determining the best way to prevent the initiation and spread of any forthcoming influenza pandemic and provide new insights into the effect of obesity on function of the immune system.